Short Access to Belt Compounds with Spatially Close C=C Bonds and Their Transannular

30 31 Two domino Diels–Alder adducts were obtained from 3,7-bis(cyclopenta-2,4-dien-1-ylidene)-cis32 bicyclo[ 3.3.0]octane and dimethyl acetylenedicarboxylate or Nmethylmaleimide under microwave 33 irradiation. From the first adduct, a C20H24 diene with C2v symmetry was obtained by Zn/AcOH 34 reduction, hydrolysis, oxidative decarboxylation, and selective hydrogenation. Photochemical [2+2] 35 cycloaddition of this diene gave a thermally unstable cyclobutane derivative, which reverts to the diene. 36 However, both the diene and the cyclobutane derivatives could be identified by X-ray diffraction 37 analysis upon irradiation of the diene crystal. New six-membered rings are formed upon the transannular 38 addition of bromine or iodine to the diene. The N-type selectivity of the addition was examined by 39 theoretical calculations, which revealed the distinct susceptibility of the doubly bonded carbon atoms to 40 the bromine attack. 41 42

Two domino Diels-Alder adducts were obtained from 3,7-bis(cyclopenta-2,4-dien-1-ylidene)-cis-32 bicyclo[ 3.3.0]octane and dimethyl acetylenedicarboxylate or Nmethylmaleimide under microwave 33 irradiation. From the first adduct, a C20H24 diene with C2v symmetry was obtained by Zn/AcOH 34 reduction, hydrolysis, oxidative decarboxylation, and selective hydrogenation. Photochemical [2+2] 35 cycloaddition of this diene gave a thermally unstable cyclobutane derivative, which reverts to the diene. 36 However, both the diene and the cyclobutane derivatives could be identified by X-ray diffraction 37 analysis upon irradiation of the diene crystal. New six-membered rings are formed upon the transannular 38 addition of bromine or iodine to the diene. The N-type selectivity of the addition was examined by 39 theoretical calculations, which revealed the distinct susceptibility of the doubly bonded carbon atoms to 40 the bromine attack. atoms do not lie in the same plane as the attached atoms.
[1] The degree of pyramidalization of these 46 carbon atoms may be large enough to confer unique structural, spectroscopic, and chemical 47 properties.
[3] Of particular interest is the formation of cyclobutane dimers, which experience 50 a thermal [2+2] retrocycloaddition to the belt dienes 4 with close parallel C=C bonds.
[3g] In turn, these 51 compounds photochemically generate the cyclobutane products and experience transannular additionsof 52 electrophiles, such as bromine, iodine, or water. 53 Because the preparation of the diiodides 1 implies many synthetic steps, the dienes 4 are not readily 54 available. Herein, we describe a short synthetic route to the dienes 8 and 9 (Scheme 2), which features a 55 key step consisting of a domino DA reaction among the known [4] difulvene 7 and dimethyl 56 acetylenedicarboxylate or N-methylmaleimide under microwave irradiation. Furthermore, several 57 transannular and photochemical transformations of these compounds are also examined. The preferential 58 formation of N-type halogenated adducts over the U-type products is investigated by means of 59 theoretical calculations. Overall, the results support the reliability of the domino Diels-Alder reaction to 60 yield polycyclic compounds with belt structures having close parallel C=C bonds. 61

RESULTS AND DISCUSSION 63 64
Reaction of equimolar amounts of the difulvene 7 and dimethyl acetylenedicarboxylate in 1,2-65 dichlorobenzene under microwave irradiation at 150 8C for 5 min gave a product mixture, which after 66 column chromatography and washing with MeOH yielded the domino DA adduct 8 in 24% yield 67 (Scheme 2). Longer or shorter reaction times of microwave irradiation led to lower yields of compound 68 8. 69 Similarly, reaction of compound 7 with N-methylmaleimide under similar conditions and treatment gave 70 adduct 9 in only 11% yield (Scheme 2). Alternatively, compound 9 was obtained by microwave 71 irradiation of a mixture of the double DA adducts of the difulvene 7 and N-methylmaleimide in 1,2-72 dichlorobenzene. The formation of compound 9 under these conditions requires that the above-described 73 double DA adducts experience a retro-DA reaction to regenerate the fulvene subunit necessary for the 74 intramolecular DA reaction. 75 Worthy of note, reaction of compound 7 and maleic anhydride or cis-and trans-1,2-76 bis(phenylsulfonyl)ethylene, under microwave irradiation conditions used to prepare compound 8, did 77 not give any defined product. This agrees with the findings by Hong et al.
[5] who reported that the 78 reaction of 7,7-dimethylfulvene and maleic anhydride under microwave irradiation did not give the 79 expected DA addition product, but adducts from tautomeric derivatives of the fulvene unit. In this work, 80 the expected DA adducts were formed under conventional thermal conditions. 81 Hydrogenation of the products 8 and 9 by using 5% Pd on charcoal led to the selective formation of 82 compounds 10 and 11, respectively.
[6] The configuration of all of these compounds was clearly 83 established by spectroscopic studies and, for compounds 8, 9, and 10, confirmed by X-ray diffraction 84 analysis (see the Supporting Information photocycloaddition of simple alkenes in the solid state and in the absence of any photosensitizer has 132 been reported before. 133 The olefinic carbon atoms of compounds 8, 9, 10, 17, and 18 are slightly pyramidalized: C4/C9 (13.5-134 15.88) and C3a/C9a (2.0-5.88).
[13] Also, the C6¢C7 (1.586-1.589 ae) and C13¢C14 bonds (1.572-135 1.588 ae) are somewhat longer than the standard C¢C bond length (see Table S2 in the Supporting 136 Information). 137 Reaction of the diene 18 with a slight molar excess of bromine or iodine in CH2Cl2 gave compounds 21 138 and 22, respectively, as the only detected products (Scheme 4). The 13C NMR data supported the Cs 139 symmetry group (N-type addition). Utype additions would have generated a five-and a sevenmembered 140 ring in the halogenated products, leading to products with C2v symmetry. X-ray diffraction analyses 141 further confirmed the structures of compounds 21 and 22 (see in Supporting Information). 142 The mechanism of the bromination addition of the diene 18 was examined by combining density 143 functional theory calculations and the self-consistent reaction field theory to account for solvation with the X-ray structure, as noted in the pyramidalization of the C=C carbon atoms (C3a/ C9a: 4.88, 150 C4/C9: 15.68), and the lengths of the C6¢C7 and C13¢C14 bonds (1.581 and 1.582 ae, respectively). 151 In the pre-reactant complex (i.e., I1 in Figure 2), the bromine atom closest to the molecule is roughly 152 equidistant (2.37-2.50 ae) from the doubly bonded carbon atoms. Addition of bromine to the carbon 153 atoms C3a and C4 is concurrent with the breaking of the bond in the Br2 molecule and with the 154 formation of bonds between the atom pairs C4¢C9a and C3a¢C9 (distances of 2.48 and 2.12 ae, 155 respectively, in the transitionstate structures (i.e., TS(3a) and TS(4) in Figure 2). The barrier for the 156 addition to the C3a atom is approximately 3.2 kcal mol¢1 more favorable than the addition to the C4 157 atom. This difference can be partly ascribed to the larger electron density supported by the C3a atom 158 relative to the C4 atom in the diene (Dq=0.034 e, Figure S1 in the Supporting Information). This process 159 leads to a N-type-brominated adduct cation, which is characterized by the presence of internal six-160 membered rings leading to a formal positive charge on the carbon atom C9. Finally, the nucleophilic 161 addition of the bromine anion to the C9 atom generates compound 21. All attempts to locate the 162 transition states leading to the U-type bromine addition were unsuccessful, suggesting that this process 163 induces a larger structural barrier than the N-type addition. The largest destabilization of the U-type 164 adduct formed upon addition to the C4 atom is reflected in the relative free energy compared to the N-165 type adducts, because the former is destabilized by around 15 kcalmol¢1 relative to the preferred N-166 type-brominated cation adduct (i.e., I3(3a) in Figure 3). This trend is also noted in the larger distance 167 between the carbon atoms of the bond formed between the two C=C bonds, and the lower value of the 168 electron density at the bond critical point (Figure 3). In addition, all attempts to locate the U-type adduct 169 originating from bromination at the C3a atom failed. 170 Bromination of the diene diester 10 was performed under similar conditions, leading to a mixture of the 171 isomeric dibromides 23 and 24. Samples of these dibromides could be obtained by slow crystallization 172 from EtOAc and were fully characterized by spectroscopic and analytical means including Xray 173 diffraction analysis. As before, only N-type addition was observed. Compound 23 was the major species 174 of the reaction mixture, which contained compounds 23 and 24 in a ratio of 3.5:1 (as obtained by 1H 175 NMR spectroscopy), an effect that can be ascribed to the inductive effect of the ester groups on the 176 double bond formed by the C3a and C4 atoms. 177 The X-ray diffraction data for most compounds described in this paper have been collected in the Tables       An aqueous NaOH solution (9.6m, 7 mL) was added dropwise to a cold (0 8C, ice/water bath) 405 suspension of a mixture of compounds 12, 13, and 14 (223 mg, 0.59 mmol) in 96% EtOH (2.4 mL), and 406 then the mixture was heated at 958C for 4 h. The mixture was allowed to cool to room temperature, was 407 acidified with 1n HCl and extracted with EtOAc (45 mL). The aqueous phase was extracted with EtOAc 408 (2Õ40 mL). The combined organic phases were washed with water (2Õ20 mL), dried with anhydrous 409 Na2SO4, and concentrated in vacuum to give a beige solid (205 mg, 92% yield), which was a h, the current diminished till 0.06 A. Water (45 mL) and EtOAc (100 mL) were added. The organic 432 phase was separated and the aqueous phase was extracted with EtOAc (2Õ100 mL). The combined 433 organic phase and extracts were washed with 1n HCl (3Õ60 mL) and water (2Õ 60 mL), dried with 434 anhydrous Na2SO4, and concentrated in vacuum to give a residue (165 mg), which was subjected to 435 column chromatography (35-70 mm silica gel (4 g), pentane/EtOAc mixtures added to a solution of the diacid 15 (561 mg, 1.60 mmol) in quinoline (9.5 mL), and the mixture was 455 heated at 1858C for 18 h. The mixture was allowed to cool to room temperature, poured onto 2n HCl 456 (50 mL), filtered through a short pad of celite. and washed with water (15 mL) and pentane (100 mL). 457 The organic phase was separated from the combined filtrate and the aqueous phase was extracted with 458 pentane (3Õ100 mL). The combined organic phases were washed with 1n HCl (2Õ80 mL) and water 459 (2Õ80 mL), dried with anhydrous Na2SO4, and distilled under atmospheric pressure by using a 10 cm 460 Vigreux column and heating till 508C. The oily residue (59.5 mg) contained the tetraene 17, 2-461 methylnaphthalene, and traces of 1-methylnaphthalene and the alcohol 16. An approximate molar ratio 462 of 17/2-methylnaphthalene of 1:2 was calculated from the integration of the signals corresponding to the 463 olefinic protons of the tetraene 17 (d=6.37 ppm) and the methyl protons of 2-methylnaphthalene (d=2.51 464 ppm) in the 1H NMR spectrum of the mixture. This residue was placed in a desiccator containing 465 paraffin wax under vacuum overnight to give the tetraene 17, containing traces of the alcohol 16 as a 466 white solid (31 mg). The combined aqueous phases were extracted with EtOAc (3Õ100 mL) and the 467 combined organic extracts were washed with 1n HCl (2Õ80 mL) and water (2Õ80 mL). The organic 468 phase was extracted with a saturated aqueous NaHCO3 solution (3Õ80 mL) and water (2Õ80 mL). The 469 organic phase was dried with anhydrous Na2SO4 and distilled under atmospheric pressure by using a 10 470 cm Vigreux column and heating till 110-1158C, to give an oily residue (127 mg) containing the tetraene 471 17, 2-methylnaphthalene, and traces of 1-methylnaphthalene and the alcohol 16 (approximate molar 472 ratio 17/2-methylnaphthalene 2:1), which was subjected to column chromatography (neutral Al2O3 (8 473 g), pentane/EtOAc mixtures). On elution with pentane a first fraction (16 mg) consisting mainly of a 474 mixture of 2-methylnaphthalene and the tetraene 17 in an approximate ratio 2-475 methylnaphthalene/tetraene 17 of 8:1, and a second fraction (32 mg) consisting mainly of the tetraene 17 476 were isolated. The second fraction, after elimination of the methylnaphthalenes, as described before, 477 gave pure the tetraene 17 (27 mg) as a white solid. On elution with pentane and pentane/EtOAc 9:1, a 478 third fraction (6 mg) containing the impure alcohol 16 was isolated. The aqueous NaHCO3 extracts 479 were acidified with 1n HCl (120 mL) and extracted with EtOAc (3Õ120 mL). The combined organic 480 phases were washed with water (2Õ80 mL), dried with anhydrous Na2SO4, and concentrated in vacuum 481 to give a solid residue (229 mg), which consisted mainly of the starting diacid 15. This product was 482 resubmitted as such to the above-described bis-decarboxylation process leading to a pentane extract (15 483 mg) and an EtOAc extract (39 mg), both containing the tetraene 17, 2-methylnaphthalene, and the 484 alcohol 16 in a 2-methylnaphthalene/tetraene 17/alcohol 16 ratio of about 4:2:1. These fractions were 485 combined and subjected to column chromatography (neutral Al2O3 (7 g), pentane/ EtOAc mixtures). On 486 elution with pentane, a mixture containing mainly 2-methylnaphthalene and the tetraene 17 (ratio 2-487 methylnaphthalene/tetraene 17 5:2, 6 mg) and the tetraene 17 ( cryoloop supported on a goniometric bolster at about 4 cm from a 125 W low-pressure mercury lamp. 538 The crystal was cooled at ¢1008C with a stream of cold nitrogen flowing from about 2 cm from the 539 upper side of the crystal, while it was irradiated for 5 h. The crystal was rotated several times to irradiate 540 it from different sites. After stopping the irradiation, the crystal was immediately submitted to X-ray 541 diffraction analysis at 100 K (exposure time: 3.87 h). The X-ray data (see part 1.7 in the Supporting 542 Information) show that the crystal contains molecules of the cyclobutane derivative 19 and the diene 18 543 in a ratio 19/18 of 1:1. 544 545 Thermal conversion of the cyclobutane 19 to the diene 18 546 The kinetics of the thermal conversion of compound 19 to compound 18 was followed by 1H NMR 547 spectroscopy in CDCl3 at 25, 35, and 458C. The ratio 19/18 was obtained by integration of the signals at 548 d=2.30 ppm corresponding to four protons (i.e. , 1(3a,4a,7)-H) of compound 19 and d=2.38-2.44 ppm 549 (complex absorption) corresponding to six protons (i.e., 6(7)-H and 3(10,12a,13a)-H) of compound 18 550 (see Table S1 in the Supporting Information was added dropwise to a stirred solution of the diene 18 (11.1 mg, 42 mmol) in anhydrous CH2Cl2 (2 562 mL) under an Ar atmosphere, and the reaction mixture was stirred at room temperature protected from 563 light for 20 h. The brown solution was diluted with CH2Cl2 (5 mL), washed with a 10% aqueous 564 solution of NaHSO3 (1Õ3 mL plus 2Õ2.5 mL) and water (3 mL), dried with anhydrous Na2SO4, and 565 concentrated in vacuum to give the crude dibromo derivative 21 as a light brown solid (19.8 mg), which 566 was crystallized from EtOAc (3 mL) to give compound 21 (16 mg, 89% yield) as a white solid. M.p. 567 Keywords: density functional calculations · domino reactions · photochemistry · polycycles · X-ray 658 diffraction 659 660